BPA and Male Reproductive Health: Mechanistic Insights, Toxicological Implications, and the Protective Role of Antioxidants.

Bisphenol A (BPA) is a ubiquitous endocrine-disrupting chemical commonly used in producing polycarbonate plastics and epoxy resins, resulting in widespread human exposure through various sources. BPA mimics estrogen and disrupts the hypothalamic-pituitary-testicular (HPT) axis, impairing androgen signaling, steroidogenesis, and spermatogenesis. It induces oxidative stress by promoting the excessive generation of reactive oxygen species (ROS), resulting in lipid peroxidation, DNA damage, mitochondrial dysfunction, and apoptosis of germ cells. BPA also compromises the antioxidant defense systems by downregulating key enzymes such as superoxide dismutase, catalase, and glutathione peroxidase, contributing to redox imbalance. BPA exposure during critical developmental windows is particularly concerning, as it can cross the placenta and has been detected in amniotic fluid, cord blood, placenta, and breast milk. Early-life exposure may have long-term consequences for male reproductive health. Furthermore, BPA-induced epigenetic modifications suggest the potential for transgenerational reproductive effects. Recent studies have demonstrated the ameliorative effects of various antioxidants, including α-lipoic acid, melatonin, selenium, vitamins, and phytochemicals, in mitigating BPA-induced testicular toxicity. These agents help to restore redox homeostasis, preserve mitochondrial integrity, and attenuate inflammation and apoptosis. This review uniquely integrates endocrine disruption, oxidative stress, mitochondrial dysfunction, and epigenetic alterations to provide a comprehensive mechanistic framework. It also highlights emerging pathways such as lipid peroxidation-mediated damage and evaluates antioxidant interventions based on their molecular targets. A comprehensive understanding of the molecular pathways underlying BPA-induced reproductive toxicity and the mechanistic basis of antioxidant-mediated protection is imperative for developing effective interventions to protect male reproductive health.